The goal of this project will be to identify and characterize serotonin (5-hydroxytryptamine; 5-HT) receptor subtypes in the central nervous system using a combination of molecular pharmacological and biochemical techniques. The project will focus on three major areas. First, an extremely detailed comparative pharmacological characterization will be made of all known 5-HT binding site subtypes using currently available radioligands. The goal is to determine a specific "pharmacological profile" for each 5-HT receptor subtype so that each subtype can be more easily identified in functional assays. Secondly, novel radioligands will be synthesized in collaboration with other investigators and an attempt will be made to either identify previously undescribed 5-HT binding site subtypes or to improve upon the methodology currently available to characterize known populations of 5-HT binding site subtypes. Finally, for each 5-HT receptor subtype identified, an attempt will be made to develop an in vitro biochemical assay in order to assess drug efficacy at the receptor. It is expected that at least 2 assays (adenylate cyclase and phosphatidylinositol turnover studies) will be used to develop these important correlations. This combination of molecular pharmacological and biochemical approaches should greatly facilitate the characterization of 5-HT receptor subtypes in the central nervous system. Increased knowledge of the pharmacological properties and biochemical effects of 5-HT receptor subtypes should clarify the role of 5-HT in both normal and abnormal human brain function.